Clinical Trial: Water and Sudafed in Autonomic Failure
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: Effect of Drinking Water on the Pressor Response to Pseudoephedrine in Patients With Autonomic Failure
Brief Summary: The specific aim of this study is to determine whether water ingestion potentiates the pressor response to pseudoephedrine in patients with primary disorders of autonomic failure. The study design will enable us to also evaluate the pressor response to water alone and to pseudoephedrine alone. In a secondary analysis, we will compare the results in patients with two autonomic disorders, pure autonomic failure (PAF) and multiple system atrophy (MSA). We hypothesize that drinking water following a dose of pseudoephedrine will lead to a greater increase in blood pressure than pseudoephedrine alone.
Detailed Summary:
The maximal pressor response to water is reached when other pressor agents are only beginning to act. In addition to the therapeutic value of water ingestion alone, the blood pressure-raising effects of agents that increase sympathetic nervous system tone, such as phenylpropanolamine, are potentiated by water drinking. These drug interaction effects can be exploited in the treatment of orthostatic hypotension with the combination of water and a sympathomimetic potentially able to increase blood pressure to a greater extent and for a longer period of time than either water or the medication alone. However, the interaction can also lead to potentially dangerous blood pressure surges.
This protocol requires an initial screening history and physical of study participants, including safety labs and EKGs, and evaluation of their autonomic nervous system status following the consent process. If the patient meets study criteria and is willing to undergo study testing, the 4-way crossover protocol will follow.
Study Testing days 1 and 2 Arm 1: Pseudoephedrine 30 mg PO + 50 ml water Arm 2: Pseudoephedrine 30 mg PO + 480 ml water
- Testing will be performed at the same time of day for all studies, at least 2 hours after a meal to avoid any confounding effects from postprandial hypotension.
- A saline lock will be inserted for blood sampling at least 30 minutes before baseline data collection.
- Participants will be asked to empty their bladders before beginning the test to avoid any effect of a full urinary bladder on peripheral sympathetic activity.
- Participants will be seated comfortably in a chair. They will be asked to remain in the seated position for
Sponsor: Vanderbilt University
Current Primary Outcome: The primary outcome measure in each Aim will be the peak increase in systolic blood pressure after pseudoephedrine or placebo relative to baseline (delta SBP). [ Time Frame: between 60 and 120 minutes after pseudoephedrine or placebo ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Change in diastolic blood pressure relative to baseline [ Time Frame: between 60 and 120 minutes after pseudoephedrine or placebo ]
- Change in heart rate relative to baseline [ Time Frame: between 60 and 120 minutes after pseudoephedrine or placebo ]
- Absolute systolic blood pressure after treatment [ Time Frame: between 60 and 120 minutes after pseudoephedrine and placebo ]
- Absolute diastolic blood pressure after treatment [ Time Frame: between 60 and 120 minutes after pseudoephedrine or placebo ]
- area under the curve for systolic blood pressure from baseline to 135 minutes post-treatment [ Time Frame: from baseline to 135 minutes after pseudoephedrine or placebo ]Area under the curve can better measure an extension of the duration of response.
- Peak plasma norepinephrine concentration after treatment [ Time Frame: between baseline and 135 minutes after pseudoephedrine or placebo ]
Original Secondary Outcome: Same as current
Information By: Vanderbilt University Medical Center
Dates:
Date Received: May 26, 2014
Date Started: October 2014
Date Completion: December 2019
Last Updated: April 3, 2017
Last Verified: October 2016
